Scientists Successfully Expand the Genetic Alphabet

Scientists have for the first time been able to build a organism containing a new, synthetic pair of DNA units, marking a breakthrough in the field of synthetic biology that has major implications for medicine.

Via Synthorx.

In case your high school biology knowledge is a bit rusty: DNA and RNA are composed of four naturally occurring nitrogenous bases, Adenine, Thymine, Guanine and Cytosine, which pair up respectively (A-T and G-C) to make base pairs that code genetic sequences. Today's breakthrough comes in the form of a new, synthetic pair (X-Y), which was added to the mix with successful results. The research, led by Denis Malyshev and Floyd Romesberg, is detailed in a paper titled "A semi-synthetic organism with an expanded genetic alphabet," published in Nature today. The New York Times explains:

[The researchers] inserted an X-Y pair into the common bacterium E. coli. The bacteria were able to reproduce normally, replicating the X and Y along with the natural nucleotides. In effect, the bacteria have a genetic code of six letters rather than four, perhaps allowing them to make novel proteins. “If you have a language that has a certain number of letters, you want to add letters so you can write more words and tell more stories,” said Floyd E. Romesberg, a chemist at Scripps who led the work.

The scientists spliced the new base-pair into E. coli and saw the bacteria successfully replicate the X-Y pair when it reproduced. According to fellow synthetic biologist Steven Benner, "this is the first time that you have had a living cell manage an alien genetic alphabet."

The researchers have already launched a company intended to monetize the discovery by using it to develop new drugs, diagnostics and vaccines, among other things. In a press release for the firm, Synthorx Inc., Dr. Romesberg explained that "the ability to incorporate and replicate a synthetic DNA base pair in vivo means that we have, for the first time, expanded the genetic alphabet to increase the amount of information that can be stored in DNA." The new company's president, Court Turner, said that:

Adding X and Y to the genetic alphabet, we now have an expanded vocabulary to generate a variety of new inputs and materials for drug discovery, improved vaccines and improvements to nanotechnologies, such as microprocessing.

The non-business synthetic biology community is also excited by the discovery. Benner told Bradley Fikes of U-T San Diego that the discovery could make it easier for others in the field to be taken seriously, saying "What you think is impossible or possible depends on how you were trained. It's a cultural statement."

Romesberg tells Fikes about his team's discovery.

This type of discovery raises the normal fears associated with artificial life, butDr. Romesberg assures the Times that the new base pair would not be able to survive in a different organism. "This could never infect something," he said.

The bacteria described in the Nature paper each contained only a single X-Y pair. It is not yet known whether a cell would function if it contained many such pairs. It is also not clear how long the bacteria will survive. The paper mentions growing them for only 24 replications over about 15 hours. Most important, the researchers have not yet demonstrated that the artificial nucleotides can be transcribed into RNA and then used to make proteins.